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Structural insights into glucose-6-phosphate recognition and hydrolysis by human G6PC1.
Proc Natl Acad Sci U S A
January 2025
Beijing National Laboratory for Condensed Matter Physics, Laboratory of Soft Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing 100190, China.
The glucose-6-phosphatase (G6Pase) is an integral membrane protein that catalyzes the hydrolysis of glucose-6-phosphate (G6P) in the endoplasmic reticulum lumen and plays a vital role in glucose homeostasis. Dysregulation or genetic mutations of G6Pase are associated with diabetes and glycogen storage disease 1a (GSD-1a). Studies have characterized the biophysical and biochemical properties of G6Pase; however, the structure and substrate recognition mechanism of G6Pase remain unclear.
View Article and Find Full Text PDFLight signal regulates endoreduplication and tomato fruit expansion through the SlPIF1a-SlTLFP8-SlCDKB2 module.
Proc Natl Acad Sci U S A
January 2025
Beijing Key Laboratory of Growth and Developmental Regulation for Protected Vegetable Crops, College of Horticulture, China Agricultural University, Beijing 100193, China.
Light serves as an energy source for cell division and expansion during fruit development. Cell expansion significantly influences fruit size and is closely linked to endoreduplication, a unique cell cycle variation characterized by DNA replication without cytokinesis. Paradoxically, under conditions of ample photosynthates, light signaling suppresses cell expansion.
View Article and Find Full Text PDFMolecular mechanism of ligand recognition and activation of lysophosphatidic acid receptor LPAR6.
Proc Natl Acad Sci U S A
January 2025
Faculty of Life Sciences and Medicine, Harbin Institute of Technology Center for Life Sciences, School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China.
Lysophosphatidic acid (LPA) exerts its physiological roles through the endothelialdifferentiation gene (EDG) family LPA receptors (LPAR1-3) or the non-EDG family LPA receptors (LPAR4-6). LPAR6 plays crucial roles in hair loss and cancer progression, yet its structural information is very limited. Here, we report the cryoelectron microscopy structure of LPA-bound human LPAR6 in complex with a mini G or G protein.
View Article and Find Full Text PDFHealth State Utility Values in Fabry Disease: Insights from the Pegunigalsidase Alfa Clinical Trials.
Adv Ther
January 2025
Cytel, Inc., Waltham, MA, USA.
Introduction: Fabry disease (FD) is a rare lysosomal storage disorder that is associated with pain and progressive damage to the renal, cardiac, and cerebrovascular systems. Enzyme replacement therapy (ERT) is one of the treatment options for FD and the most recently approved ERT agent, pegunigalsidase alfa, has shown clinical efficacy in three phase 3 clinical trials of adults with FD: BALANCE, BRIDGE, and BRIGHT. Recent published guidelines support the mapping of health utility state data to the EuroQol-5 Dimension-3 Level (EQ-5D-3L) index to align with the preferred methodology used by the National Institute for Health and Care Excellence (NICE).
View Article and Find Full Text PDFAlteration of the Catalytic Properties of the Epoxyalcohol Synthase CYP443D1 (NvEAS) of the Starlet Sea Anemone Nematostella vectensis as a Result of a Single Amino Acid Substitution.
Dokl Biochem Biophys
January 2025
Kazan Institute of Biochemistry and Biophysics, Federal Research Center "Kazan Scientific Center of the Russian Academy of Sciences,", 420111, Kazan, Russia.
Cytochromes of the P450 superfamily are widespread in nature; they were found in all studied aerobic organisms. Although the degree of similarity between cytochromes P450 of different families is low, all enzymes of this superfamily have similar tertiary structures. In addition, all cytochromes P450, including enzymes of the CYP74 clan, contain substrate recognition sites in their sequences, which form the catalytic center.
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